Trabecular Area Research Articles

Effects of joint immobilization and treadmill exercise on marrow adipose tissue and trabecular bone after anterior cruciate ligament reconstruction in the rat proximal tibial epiphysis

Marrow adipose tissue (MAT) adversely affects bone metabolism under certain conditions. Although mechanical stress is an important factor in regulating MAT and bone mass, how stress from different rehabilitation protocols after anterior cruciate ligament (ACL) reconstruction affects trabecular bone and MAT is unclear. We aimed to examine the effects of joint immobilization and treadmill exercise on trabecular bone and MAT after ACL reconstruction. Rats received unilateral knee ACL transection and reconstruction surgery. After surgery, rats were reared without intervention, with joint immobilization, or with treadmill exercise (12 m/min, 60 min/day, six days/week), with untreated rats as controls. At two or four weeks after starting experiments, we examined histological changes in trabecular bone and MAT in the proximal tibial epiphysis. After ACL reconstruction, there were no significant changes in trabecular bone area and MAT area at both time points. Joint immobilization after ACL reconstruction resulted in reduced trabecular bone area and MAT accumulation due to adipocyte hyperplasia and hypertrophy within four weeks. Treadmill exercise after ACL reconstruction did not affect any parameters in trabecular bone and MAT. We detected a moderate negative correlation between trabecular bone area and MAT area. Therefore, MAT accumulation induced by joint immobilization may contribute, at least in part, to reducing trabecular bone area. To minimize trabecular bone loss and MAT accumulation, joint immobilization after ACL reconstruction should be minimized. Exercise after ACL reconstruction did not alter trabecular bone and MAT.

Long-term effects of mild cataract extraction versus laser peripheral iridotomy on anterior chamber morphology in primary angle-closure suspect eyes

AimTo compare lens extraction (LE) and laser peripheral iridotomy (LPI) on anterior segment morphology in primary angle-closure suspect (PACS) eyes.MethodsThis prospective clinical trial included 144 patients with PACS who underwent...

Rho Kinase Inhibitor AR-12286 Reverses Steroid-Induced Changes in Intraocular Pressure, Effective Filtration Areas, and Morphology in Mouse Eyes.

We investigated mechanisms of reduction of intraocular pressure (IOP) by Rho kinase inhibitor AR-12286 in steroid-induced ocular hypertension (SIOH). C57BL/6 mice (N = 56) were randomly divided into Saline, dexamethasone (DEX), DEX + AR-12286, and DEX-discontinuation (DEX-DC) groups. IOP was measured weekly during the first four weeks in all groups. Beginning at week 5, the DEX-DC group was followed without treatment until IOP returned to normal, and the other groups were treated as assigned with IOP measured every other day for another week. Fluorescent tracer was injected into the anterior chamber to visualize the outflow pattern in the trabecular meshwork (TM) and TM effective filtration area (EFA) was determined. Radial sections from both high- and low-tracer regions were processed for electron microscopy. AR-12286 reduced IOP in SIOH mouse eyes in one day (P < 0.01). At the end of week 5, mean IOP in the DEX + AR-12286 group was ∼4 mm Hg lower than DEX group (P < 0.001) and ∼2 mm Hg lower than DEX-DC group (P < 0.05). After one-week AR-12286 treatment (P < 0.05) or five-week DC of DEX (P < 0.01), DEX-induced reduction of EFA was rescued and DEX-induced morphological changes in the TM were partially reversed. AR-12286 reversed steroid-induced morphological changes in the TM and reduced EFA, which correlated with reduced IOP in SIOH eyes. AR-12286 reduced IOP elevation in SIOH eyes more effectively than discontinuing DEX treatment even when accompanied by continuous DEX treatment. Therefore Rho kinase inhibitors may lower SIOH in patients who rely on steroid treatment.

Associations Between Inflammatory Mediators and Bone Outcomes in Postmenopausal Women: A Cross-Sectional Analysis of Baseline Data from the Prune Study.

Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during postmenopausal osteoporosis. This study aimed to investigate the association between circulating inflammatory markers and bone outcomes in postmenopausal women. We conducted a cross-sectional, secondary analysis of baseline data from participants who completed a 12-month randomized controlled trial, The Prune Study (NCT02822378), which included healthy postmenopausal women (n=183, 55-75 years old) with bone mineral density (BMD) T-score between 0.0 and -3.0 at any site. BMD was measured using dual-energy X-ray absorptiometry, and bone geometry and strength were measured using peripheral quantitative computed tomography. Blood was collected at baseline to measure (1) serum biomarkers of bone turnover, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide and (2) inflammatory markers, including serum high-sensitivity C-reactive protein (hs-CRP) and plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1, using enzyme-linked immunosorbent assay. The associations between bone and inflammatory outcomes at baseline were analyzed using correlation and regression analyses. Serum hs-CRP negatively correlated with P1NP (r=-0.197, p=0.042). Plasma IL-1β, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all p<0.05). In normal-weight women, plasma IL-1β, IL-6, and IL-8 negatively correlated (p<0.05) with trabecular and cortical bone area, content, and density at various sites in the tibia and radius. Serum hs-CRP positively predicted lumbar spine BMD (β=0.078, p=0.028). Plasma IL-6 negatively predicted BMD at the total body (β=-0.131, p=0.027) and lumbar spine (β=-0.151, p=0.036), whereas plasma TNF-α negatively predicted total hip BMD (β=-0.114, p=0.028). At baseline, inflammatory markers were inversely associated with various estimates of bone density, geometry, and strength in postmenopausal women. These findings suggest that inflammatory markers may be an important mediator for postmenopausal bone loss.

Swept-source optical coherence tomography and ultrasound biomicroscopy study of anterior segment parameters in primary angle-closure glaucoma.

To evaluate the agreement between swept-source OCT (CASIA2) and UBM in primary angle-closure glaucoma. Eighty eyes of 40 participants diagnosed with primary angle-closure glaucoma were examined. Parameters measured included angle opening distance (AOD), angle recess area (ARA), trabecular iris space area (TISA), trabecular iris angle (TIA), lens vault (LV), anterior chamber depth (ACD), and anterior chamber width (ACW). Angle images of nasal, temporal, superior, and inferior were acquired by the anterior segment mode of CASIA2 and UBM. One-way analysis of variance and paired t-test were used for statistical analysis, and the agreement was analyzed by internal correlation coefficient (ICC) and Bland-Altman method. One-way ANOVA pairwise comparison showed that CASIA2 or UBM had the narrowest superior chamber angle and the widest temporal chamber angle in patients with primary angle-closure glaucoma. The paired t-test showed that inter-device AOD, TIA, ARA, and TISA of superior chamber angle had significant differences (p < 0.001). There was no significant difference in the measured values of LV, ACD, and ACW (p > 0.05). The agreement of all parameters is good through the Bland-Altman method comparison. ICC result showed moderate agreement in other angle parameters except for superior ARA500 (0.739). In the anterior chamber angle measurement process, we should pay more attention to the superior chamber angle covered by eyelids. Although the agreement is acceptable between CASIA2 and UBM, the measurements could not be considered interchangeable due to the tremendous statistical difference between the two devices.

Iodine-125 brachytherapy suppresses tumor growth and alters bone metabolism in a H1299 xenograft mouse model.

The present study aimed to investigate the efficacy of Iodine-125 (I-125) brachytherapy in a mouse model of non-small cell lung cancer, to further explore the efficacy and appropriate method of implantation of the I-125 radioactive seed. This study also aimed to determine the impact of brachytherapy on bone metabolism. A total of 18 mice were used to establish H1299 xenograft models, and were randomly assigned to three groups. These included non-radioactive seed implantation (Sham IM), fractionated I-125 seed implantation (Fractionated IM) and single I-125 seed implantation (Single IM) groups. Mice were euthanized after 28days of implantation. H&E staining, Ki67 immunohistochemistry, CD31 morphometric analysis and TUNEL immunofluorescence assays were respectively used to determine the histopathological changes, proliferation, micro-angiogenesis and apoptosis of tumors. In addition, bone volume and microstructure were evaluated using trabecular bone area (Tb.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and cortical thickness. Bone metabolic status was analyzed using histomorphometric staining of tartrate-resistant acid phosphate (TRAP) and alkaline phosphatase (ALP) expression in the femur, and using an ELISA assay to determine the expression of C-telopeptide of type 1 collagen (CTX-1) and procollagen type 1 n-terminal propeptide (P1NP) in the serum. Moreover, reverse transcription-quantitative PCR and western blotting were carried out for the analysis of bone remodeling-related gene expression in the bone tissue. Results of the present study demonstrated that compared with the Sham IM group, both the I-125 seed implantation groups, including Fractionated IM and Single IM, demonstrated significant therapeutic effects in both tumor volume and weight. More specifically, the most significant therapeutic effects on tumor inhibition were observed in the Fractionated IM group. Results of Ki67 and CD31 immunohistochemical staining suggested a notable reduction in tumor cell proliferation and micro-angiogenesis, and results of the TUNEL assay demonstrated an increase in tumor cell apoptosis. Although the cortical bone appeared thinner and more fragile in both I-125 seed implantation groups, no notable adverse changes in the morphology of the cancellous bone were observed, and the index of Tb.Ar, Tb.Th and Tb.n was not significantly different among Sham IM and I-125 implantation groups. However, alterations in bone metabolism were characterized by a decrease in CTX-1 and P1NP expression, accompanied by an increase in TRAP activity and a decrease in ALP activity. Results of the present study also demonstrated the notable suppression of osteocalcin and runt-related transcription factor 2. I-125 seed implantation may be an effective and safe antitumor strategy. Moreover, the use of fractionated implantation patterns based on tumor shape exhibited improved therapeutic effect on tumor suppression when the total number of I-125 seeds was equivalent along with reduced complications associated with bone loss.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.

C-reactive protein predicts endocortical expansion but not fracture in older men: the prospective STRAMBO study.

Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant. We studied the association of the hsCRP with the prospectively assessed decrease in areal bone mineral density (aBMD), bone microarchitecture decline, and fracture risk in older men. At baseline, hsCRP was measured in 823 men aged 60-88. Areal BMD and bone microarchitecture (distal radius, distal tibia) were assessed by dual-energy X-ray absorptiometry and high-resolution peripheral QCT, respectively, at baseline and after 4 and 8years. Data on incident fractures were collected for 8years. Higher hsCRP concentration was associated with faster increase in aBMD at the whole body and lumbar spine, but not other sites. Higher hsCRP levels were associated with faster decrease in cortical area and more rapid increase in trabecular area at the distal radius (0.048 mm2/year/SD, p < 0.05) and distal tibia (0.123 mm2/year/SD, p < 0.001). At the distal tibia, high hsCRP level was associated with greater decrease in total and cortical volumetric BMD (vBMD) and in failure load. The hsCRP levels were not associated with the fracture risk, even after accounting for competing risk of death. Higher hsCRP levels were associated with greater endocortical expansion at the distal radius and tibia. Higher hsCRP was associated with slightly faster decrease in total and cortical vBMD and failure load at distal tibia, but not with the fracture risk. Thus, high hsCRP levels are associated with faster cortical bone loss, but not with fracture risk in older men.

Peripheral quantitative computed tomography-derived bone parameters in men with impaired fasting glucose and diabetes.

Individuals with type 2 diabetes mellitus (T2DM) are at higher risk of fracture, but paradoxically do not have reduced bone mineral density. We investigated associations between peripheral quantitative computed tomography (pQCT) and glycaemia status. Participants were men (n = 354, age 33-92year) from the Geelong Osteoporosis Study. Diabetes was defined by fasting plasma glucose (FPG) ≥ 7.0mmol/L, self-report of diabetes and/or antihyperglycaemic medication use and impaired fasting glucose (IFG) as FPG 5.6-6.9mmol/L. Bone measures were derived using pQCT (XCT2000) at 4% and 66% radial and tibial sites. Linear regression was used, adjusting for age, body mass index and socio-economic status. At the 4% site, men with T2DM had lower adjusted bone total area, trabecular area and cortical area at the radius (all -6.2%) and tibia (all -6.4%) compared to normoglycaemia. Cortical density was higher for T2DM at the radius (+ 5.8%) and tibia (+ 8.0%), as well as adjusted total bone density at the tibial site (+ 6.1%). At the 66% site, adjusted total bone area and polar stress strain index were lower for T2DM at the radius (-4.3% and -8.0%). Total density was also higher for T2DM (+ 1.2%). Only cortical density at the 4% tibial site was different between IFG and normoglycaemia in adjusted analyses (+ 4.5%). Men with T2DM had lower total bone area, trabecular area, cortical area and polar stress strain index than the other two groups; however, total density and cortical density were higher. Only one difference was observed between IFG and normoglycaemia; increased tibial cortical density.

Associations between body composition, physical activity, and diet and radial bone microarchitecture in older adults: a 10-year population-based study.

To describe associations between exposures of lean mass and fat mass, dietary patterns, serum 25-hydroxyvitamin D (25(OH)D), physical activity and grip strength, and bone outcome measures including bone mineral density and microarchitecture in older adults. Data on 201 older adults (mean age 72years, female 46% at 10.7-year follow-up (phase 4) from a population-based cohort study collected at baseline and follow-up at 2.6 (phase 2), 5.1 (phase 3), and 10.7years (phase 4) were analyzed. Exposures were lean and fat mass, dietary patterns, physical activity (steps per day), serum 25(OH)D concentrations, and grip strength during follow-ups. Bone measures at phase 4 including areal bone mineral density (aBMD) at the spine, hip, and whole body by dual-energy X-ray absorptiometry, and radial cortical and trabecular bone microarchitecture by high-resolution peripheral computed tomography (HRpQCT). The cumulative average values of exposures were calculated. Multivariable linear regression was used to analyze associations between exposures and bone measures. Lean mass was beneficially associated with the hip, spine, and total body aBMD, radial cortical and trabecular bone area, and trabecular number and separation (β ranged from - 0.39/standard deviation (SD) to 0.73/SD). Fat mass was detrimentally associated with radial compact cortical and inner transitional zone bone area, vBMD, and porosity (β ranged from - 0.21 to 0.22/SD). Western dietary pattern scores were detrimentally associated with radial total and cortical bone vBMD and porosity (β ranged from - 0.20 to 0.20/SD). Steps per day were beneficially associated with inner transitional zone area and thickness (β = 0.12/SD and 0.19/SD), but no other measures. Grip strength and serum 25(OH)D were not associated with any radial bone measures. Lean mass was beneficially associated with aBMD, radial bone area, and trabecular bone microarchitecture. Fat mass had detrimental associations with radial bone area, vBMD, and porosity. A western dietary pattern was detrimental for radial bone microarchitecture while more steps per day (but not grip strength or 25(OH)D) appeared beneficial.

A Computed Tomography-based Radiomics Nomogram for Predicting Osteoporotic Vertebral Fractures: A Longitudinal Study.

Fractures are a serious consequence of osteoporosis in older adults. However, few longitudinal studies have shown the role of computed tomography (CT)-based radiomics in predicting osteoporotic fractures. We evaluated the performance of a CT radiomics-based model for osteoporotic vertebral fractures (OVFs) in a longitudinal study. A total of 7906 individuals without OVF older than 50 years, and who underwent CT scans between 2016 and 2019 were enrolled and followed up until 2021. Seventy-two cases of new OVF were identified. A total of 144 people without OVF during follow-up were selected as controls. Radiomics features were extracted from baseline CT images. CT values of trabecular bone, and area and density of erector spinae were determined. Cox regression analysis was used to identify the independent associated factors. The predictive performance of the nomogram was assessed using the receiver operating characteristic curve, calibration curve, and decision curve. CT value of vertebra (adjusted hazard ratio (aHR) = 2.04; 95% CI, 1.07-3.89), radiomics score (aHR = 6.56; 95% CI, 3.47-12.38), and area of erector spinae (aHR = 1.68; 95% CI, 1.02-2.78) were independently associated with OVF. Radscore was associated with severe OVF (aHR = 6.00; 95% CI, 2.78-12.93). The nomogram showed good discrimination with a C-index of 0.82 (95% CI, 0.77-0.87). The area under the curve of nomogram and radscore were both higher than osteoporosis + muscle area for 3-year and 4-year risk of fractures (P < .05). The decision curve also demonstrated that the radiomics nomogram was useful. Bone radiomics is associated with OVF, and the nomogram based on radiomics signature and muscle provides a tool for the prediction of OVF.

Histomorphometric analysis of osteocyte density and trabecular structure of 92 vertebral bodies of different ages and genders

BackgroundKnowledge of the histomorphometric structure of the vertebral body and factors influencing the structure is essential for a fundamental understanding of osteoporosis and osteoporotic fractures. The present study is focused on osteocyte density - a parameter seldom investigated so far – and trabecular width as well as bone area over tissue area in human vertebral bodies. MethodsNinety-two vertebral body specimens (C5, C6, Th8, Th12, L1, L2) from 12 males and seven females were studied (Ethics Application Number A 2017–0072). The prepared vertebral specimens were extracted from the ventral aspect with a Jamshidi needle®. The punches were decalcified and subsequently H&E stained. Using the Fiji/Image J program (version 1.53 f, Wayne Resband, National Institute of Mental Health, USA), osteocyte numbers were counted per calcified bone surface, and the trabecular width and bone area of trabecular bone were measured. The collected data were analyzed using the statistical software package SPSS, version 23.0 (SPSS Inc., Chicago, USA). Pearson’s correlation coefficient was used for correlation analyses. Multiple linear regression analyses were also performed. ResultsOsteocyte density did not differ significantly in comparisons based on gender and age (≤65 years; ≥66 years). Men had wider trabeculae (p < 0.001) and a higher bone area over tissue area (BA/TA, %) (p = 0.025) than women. Individuals over 65 years of age had thinner trabeculae (p < 0.001) and a smaller BA/TA (%) (p < 0.001) than younger individuals. Multiple linear regression analyses were performed to determine the influence of 'gender' and 'age' on trabecular width and bone area over tissue area. The R² was 0.388 for trabecular width and 0.227 for BA/TA (%). Per year of life, trabecular width decreases by 0.368 µm (β < 0.001) and BA/TA (%) by 0.001% (β = 0.001). Men have on average 8.2 µm wider trabeculae than women (β = 0.035). A negative correlation (r = −0.275) was observed between trabecular width and osteocyte density. The wider the trabeculae, the fewer osteocytes per mm² (p = 0.008). ConclusionsSurprisingly, we found no difference in osteocyte density with reference to age or gender. However, we did register significant age- and gender-related differences in bone area over tissue area and trabecular thickness. The age-related differences were more pronounced, implying that age-dependent loss of bone structure may be more important than differences between genders.

Elevated IGF-1 and GH Levels Are Correlated With a Thicker Iris and Wider Anterior Chamber Angle in Treatment-Naïve Acromegaly Patients.

To compare the difference in anterior segment biometrics derived from anterior segment optical coherence tomography (AS-OCT) between treatment-naïve acromegaly patients and normal controls and evaluate the correlations between above biometrics and insulin-like growth factor 1 (IGF-1) and growth hormone (GH) levels. Sixty eyes of 30 acromegaly patients and 60 eyes of 30 normal controls were included in this case-control study. Central corneal thickness, pupil diameter, iris thickness (IT), iris curvature (IC), anterior chamber depth (ACD), anterior chamber width, lens vault (LV), angle open distance (AOD) 500, AOD750, and trabecular iris space area (TISA) 500 and TISA750 were measured by AS-OCT. General linear regression models were constructed to evaluate the independent endocrine factors affecting iris morphology and anterior chamber angle (ACA) width. The acromegaly patients had an evenly thicker iris (P &lt; 0.001), a smaller IC (P &lt; 0.05), a smaller LV (P = 0.040) and significantly larger AOD500, AOD750, TISA500 and TISA750 (P &lt; 0.001). There was a positive correlation between the serum GH level and ACD in the acromegaly patients (P = 0.031). Linear regression models showed the lower LV and smaller IC were independent influencing factors of the increase in the AOD500, AOD750, and TISA750 and nasal TISA500. Serum IGF-1 was an independent factor for the increase in pupil diameter (β = 0.002, P = 0.031) and both the average nasal (β = 6.781*10-5, P = 0.049) and temporal (β = 7.736*10-5, P = 0.045) IT values and for the decrease in temporal IC (β &lt; 0.001, P = 0.037). GH was an independent factor for the increase in temporal AOD750 (β = 0.001, P = 0.030) and temporal TISA750 (β = 0.002, P = 0.016). Patients with acromegaly have a thicker IT, smaller IC, and lower LV with a wider ACA than normal controls. Serum GH is independently correlated with the temporal ACA width, whereas serum IGF-1 is independently correlated with IT, pupil diameter, and IC.

Assessment of Iris Trabecular Contact in Eyes with Gonioscopic Angle-Closure

To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. Multicenter, prospective study. A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500= 0 mm and (2) TISA500= 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500= 0 mm) to 84.7% (TISA500= 0 mm2), and the specificity was 85.7% (for both AOD500= 0 mm and TISA500= 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500= 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500= 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.

Low-intensity pulsed ultrasound partially reversed the deleterious effects of a severe spinal cord injury-induced bone loss and osteoporotic fracture healing in paraplegic rats.

To evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on the quality of femoral fracture callus formation in rats with severe osteoporosis secondary to spinal cord injury (SCI). Forty-five male rats were equally divided into three groups: the Sham group underwent sham surgery for SCI followed by surgery for femoral fracture on day ten post-spine surgery; the SCI group sustained a complete transection of the spinal cord and a femoral fracture ten days post-SCI; and the SCI group treated with ultrasound (SCI + US), which also sustained a femoral fracture on day ten post-SCI, concomitant with daily application of LIPUS at the fracture site. At the non-fractured tibias, LIPUS counteracted the SCI-induced bone loss by normalizing the osteoblastic-related gene expression, decreasing resorptive area, increasing trabecular area, and decreasing RANK and RANK-L-positive areas, which resulted in higher cortical volume and stronger tibias. Likewise, LIPUS was effective at restoring bone fracture healing in SCI rats; by promoting endochondral ossification, increasing collagen deposition and OPG-positive-area, decreasing resorptive area, which led to higher density and improved microarchitecture, ultimately resulting in stronger fracture callus. At the tibias, LIPUS counteracted the SCI-induced bone loss effects by simultaneously increasing bone formation and decreasing bone resorption. We also evidenced the osteogenic effects of LIPUS at partially restoring the endochondral ossification during callus formation, leading to a newly formed tissue with improved microarchitecture and mechanical integrity. Therefore, LIPUS may be an efficient and non-invasive approach to prevent bone loss and osteoporotic fracture in SCI individuals.

Histological Evaluation of the Effect of Local Application of Punica granatum Seed Oil on Bone Healing.

Background Bone healing is a complex and dynamic process that represents a well-orchestrated series of biological events of cellular recruitment, proliferation, and differentiation. The use of medicinal plants in bone healing has attracted increasing interest because of their lower side effects. Punica granatum seed oil (PSO) contains high levels of phenolic compounds, promotes osteoblast function, and plays an important role in bone remodeling. A gelatin sponge (Spongostan) is a hemostatic agent that is extensively applied as scaffolds in engineering and as drug carriers in the medical field. This study aimed to evaluate the effectiveness of PSO for bone healing enhancement. Twenty adult male New Zealand rabbits, weighing an average of 1.5–2 kg, were used in this study. Three intrabony holes were created in the tibiae of each animal, which were filled with a gelatin sponge (GS group) and combined gelatin sponge and PSO (GS/PSO group). Holes without material application were designated as the control group (C group). The animals were sacrificed at the healing duration (2–4 weeks) to prepare bone specimens for histological and histomorphometric analyses. Results Histological findings indicated that the bone defects in the GS/PSO group showed more bone formation, mineralization, and maturation compared with the C and GS groups. Multiple group differences for bone cells showed a highly significant difference among all groups in the 2- and 4-week healing periods except for the C/GS and GS/GS/PSO groups at 4-weeks duration. Furthermore, highly significant results were obtained between both durations regarding the trabecular area, trabecular number, and bone marrow area. Conclusion The study revealed that the combined application of GS and PSO was more effective in enhancing bone regeneration and accelerating bone healing compared with the other groups.

Taohong Siwu Decoction Promotes Osteo-Angiogenesis in Fractures by Regulating the HIF-1α Signaling Pathway.

Background Vascular damage is a major consequence of bone fracture. Taohong Siwu decoction (TSD) can raise the expression of vascular endothelial growth factor (VEGF) in fracture healing. However, its molecular mechanism in promoting angiogenesis is still unknown. The aim of this study was to investigate the potential mechanisms of TSD in the regulation of osteo-angiogenesis in fracture healing. Methods A rat tibial fracture model was established. After low- (4.5 g·kg−1), medium- (9 g·kg−1), and high-dose TSD (18 g·kg−1) and panax notoginsenoside (25 mg kg−1) treatment, hematoxylin-eosin staining was employed to visualize pathological changes in bone tissues. The levels of cytokines (interleukin (IL)-2, tumor necrosis factor-α (TNF-α), IL-6, and IL-1β), thromboxane B2 (TXB2), and 6 ketone prostaglandin F1α (6-Keto-PGF1α) were quantified by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to identify the rat aortic endothelial cells (RAECs). Control serum, 10% TSD-containing serum, and 10% TSD-containing serum combined with hypoxia-inducible factor-1α (HIF-1α) inhibitor were used to treat the RAECs and rat osteoblasts. Transwell migration assay was utilized to examine the migration of the RAECs. The Matrigel tubulogenesis assay was used for the assessment of angiogenesis. The expression of angiogenesis- (von Hippel-Lindau tumor suppressor (VHL), HIF-1α, VEGF, angiopoietin-2 (Ang-2), and pVHL) and osteogenesis-related (alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin-1 (OPN-1)) protein and gene was detected by western blot and quantitative real-time PCR (qRT-PCR). Results Compared with the model group, TSD increased the trabecular bone areas, numbers, and thicknesses in fractured rats. In the plasma, the levels of cytokines and TXB2 in the middle- and high-dose TSD group were significantly lower than those in the model group (P < 0.01). The 6-keto-PGF1α content was increased by middle- and high-dose TSD intervention (P < 0.01). Compared to the control serum group, the angiogenesis and migration of the RAECs were enhanced in the TSD group (P < 0.001). The expression of HIF-1α, VEGF, and Ang-2 in the TSD group upregulated significantly (P < 0.001). VHL and pVHL were inhibited under TSD-containing serum treatment (P < 0.001). ALP, Runx2, and OPN-1 were increased obviously in the TSD group (P < 0.001). Nevertheless, the HIF-1α inhibitor reversed these changes (P < 0.001). Conclusion TSD promotes angiogenesis and osteogenesis by regulating the HIF-1α signaling pathway. Meanwhile, it can effectively reduce the risk of inflammation and improve blood circulation.

Clinical significance and prognosis of solid / trabecular component areas of papillary thyroid carcinoma

Clinical significance and prognosis of solid / trabecular component areas of papillary thyroid carcinoma

Anterior segment parameters on optical coherence tomography in healthy South Asian children

PurposeHigh resolution spectral domain optical coherence tomography (SD-OCT) was used to assess the anterior segment structure parameters in healthy South Asian children. Methods108 eyes of 54 healthy children ≤ 16 years were recruited after a thorough eye exam. The anterior segment analysis was be done by Optopol Revo 80 high resolution SD-OCT. Central corneal thickness (CCT), Angle opening distance (AOD), Anterior chamber (AC) angle, Trabecular iris space area (TISA), Trabecular iris angle (TIA), iris thickness at 2 mm, internal AC diameter and lens vault were evaluated. ResultsMean age was 11.38 years. Mean IOP was 13.63 mmHg, mean axial length, 22.82 mm, mean spherical equivalent, -0.14 D, mean CCT, 532.6 µm and mean CDR was 0.31. The mean internal AC diameter was 11609.15 µm. The nasal and temporal AC angles was 53.54° and 50.37°, respectively [P = .033]. The nasal and temporal AOD500 were 0.9 mm and 0.85 mm, respectively [P = .629]. The nasal and temporal AOD750 were 1.21 mm and 1.06 mm, respectively [P = .583]. The nasal TIA was 41.75°; the temporal TIA; 40.24° [P = .325]. The nasal TISA500 was 0.33 mm2; the temporal TISA500, 0.31 mm2 [P = .012]. The nasal TISA750 was 0. 59 mm2; the temporal TISA750, 0.56 mm2 [P = .746]. The nasal iris thickness at 2 mm was 483.54 µm; the temporal iris thickness, 505.8 µm [P = .273]. The mean lens vault was -519.58 µm. ConclusionsOur study data depicts the normal anterior segment parameters in healthy Pakistani children.

Fluoxetine improves bone microarchitecture and mechanical properties in rodents undergoing chronic mild stress – an animal model of depression

Depression is one of the most prevalent mental disorders associated with reductions in bone mineral density and increased fracture risk. Fluoxetine is a highly prescribed selective serotonin reuptake inhibitor (SSRI) in the treatment of depression and is reported to be a risk factor for fractures. The present study examined the effect of fluoxetine on bone microarchitecture and the mechanical properties under chronic mild stress (CMS), a rodent model of depression. Thirty-one 6–9 week-old rats were allocated to 4 groups: 1) CMS + fluoxetine group (n = 10), 2) fluoxetine-only group (n = 5), 3) CMS + placebo group (n = 10) and 4) control group (no CMS and treatment) (n = 6). After 16 weeks, bone microarchitecture of the distal femur was analyzed by µCT. Mechanical properties were assessed by the three-point bending test, and antidepressant efficacy was determined by sucrose preference and forced swimming tests. Significant correlations were found between volume of sucrose intake and bone volume/tissue volume (BV/TV) (p = 0.019) and elastic absorption energy (p = 0.001) in the fluoxetine only group. The fluoxetine-only group showed significantly higher in the second moment of area in y-direction (p = 0.0298), horizontal outer diameter (mm) (p = 0.0488) and average midshaft thickness (mm) (p = 0.00047) than control group. Comparing with the control group, there was a significant reduction in trabecular number (Tb.N) in the CMS + fluoxetine group (p = 0.026) but not the fluoxetine-only group (p > 0.05). Significant increases in trabecular separation were observed in the metaphysis of CMS + placebo (p = 0.003) and CMS + fluoxetine (p = 0.004) groups when compared to the control group but not in the fluoxetine-only group (p > 0.05). During the three-point bending test, the fluoxetine-only group demonstrated significantly higher structural strength than controls (p = 0.04). Micro computed tomography (µCT) slices showed loss of trabecular bone in the metaphysis region of the CMS + fluoxetine and CMS + placebo groups but not the fluoxetine-only and control groups. In an animal model of depression, the adverse effect on the bone microarchitecture was caused by CMS but not by fluoxetine. Without exposure to CMS, fluoxetine significantly increased the cross-sectional area, trabecular bone area, structural strength and osteoblasts / bone area as compared to control condition.